cd19-directed chimeric antigen receptor (car) t-cell therapy for relapsed/refractory b-lineage leukaemia / lymphoma - a feasibility protocol

Conditions: Lymphoblastic Leukemia; Lymphoblastic Leukemia in Children; Lymphoblastic Leukemia, Acute Adult; B-cell Acute Lymphoblastic Leukemia; Large B-cell Lymphoma; CAR

Summary: the purpose of this study is to describe feasibility of delivering point-of-care manufactured cd19-directed car t-cell therapy to patients with relapsed/ refractory b-lineage leukaemia/ lymphoma.

this is a single arm, open-label, multi-center, phase ii feasibility study to deliver point-of-care manufactured cd19-directed car t-cell therapy to patients with relapsed / refractory b-lineage leukaemia / lymphoma. the study consists of the following phases: 1. screening phase: eligibility; enrolment 2. preparatory phase: bridging therapy (if required); leukapheresis; car t manufacturing; lymphodepletion. 3. treatment phase: infusion of single dose of anti-cd19 car t-cells 4. follow-up phase: efficacy and safety monitoring up to 24 months

Eligibility criteria:
inclusion criteria: 1. eligible disease conditions: 1. relapsed or refractory b-cell all (all must be satisfied) * presence of lymphoblasts in bone marrow aspirate by morphologic assessment or positive minimal residual disease at screening. * relapsed or refractory or ineligible for hsct * for relapsed b-all: documentation of cd19 tumour expression (e.g. by flow cytometry) demonstrated in bone marrow or peripheral blood within 3 months of study entry 2. relapsed or refractory large b-cell lymphoma after two or more lines of systemic therapy, including diffuse large b-cell lymphoma (dlbcl) not otherwise specified, primary mediastinal large b-cell lymphoma, high grade b-cell lymphoma, and dlbcl arising from follicular lymphoma. 2. age at screening: 1. \< 18 years (paediatric group); or 2. ≥ 18 years (adult group) 3. adequate organ functions: 4. life expectancy more than 12 weeks. 5. karnofsky (age ≥ 16 years) or lansky (age \< 16 years) performance status ≥ 50 at screening. 6. must meet the institutional criteria to undergo leukapheresis or have a leukapheresis product of non-mobilized cells received and accepted by the manufacturing site. exclusion criteria: patients with any of the following will be excluded: * b-all with isolated extramedullary disease relapse * patients with concomitant genetic syndrome: such as patients with fanconi anaemia, kostmann syndrome, shwachman syndrome or any other known bone marrow failure syndrome. patients with down syndrome will not be excluded. * patients with burkitt's lymphoma/leukaemia (i.e. patients with mature b-cell all; leukaemia with b-cell \[sig positive and kappa or lambda restricted positivity\] all, with fab l3 morphology and /or a myc translocation) * active or latent hepatitis b or active hepatitis c (test within 8 weeks of screening), or any uncontrolled infection at screening * human immunodeficiency virus (hiv) positive test within 8 weeks of screening * presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (gvhd) * active cns involvement by malignancy, defined by cns-3 per nccn guidelines. subjects with cns-2 involvement or with history of cns disease that have been actively treated are eligible. * patient has an investigational medicinal product within the last 30 days prior to screening. * pregnant or nursing women. * women of childbearing potential (defined as all women physiologically capable of becoming pregnant) and all male participants, unless they are using highly effective methods of contraception for a period of 1 year after the car t-cell infusion. all female patients of childbearing potential must have a negative pregnancy test performed within 48 hours before infusion of car t-cells. the following are not strictly exclusion criteria but must be discussed with pi/site-pi: * prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease * treatment with any prior gene therapy product * has had treatment with any prior anti-cd19/anti-cd3 therapy, or any other anti-cd19 therapy

Keywords: car t-cell therapy relapse/refractory b-all b-lineage lymphoma